tbuckley/cabot-search huggingface dataset:
Combining loop and thiazide diuretics for acute heart failure across the estimated glomerular filtration rate spectrum: A post‐hoc analysis of the <scp>CLOROTIC</scp> trial
Authors: Joan Carles Trullàs, José Luís Morales‐Rull, Jesús Casado, Margarita Carrera‐Izquierdo, Marta Sánchez‐Marteles, Alicia Conde‐Martel, Melitón Francisco Dávila‐Ramos, Pau Llácer, Prado Salamanca‐Bautista, David Chivite, Rosa Jordana‐Comajuncosa, Maria Villalonga, María Inmaculada Páez‐Rubio, Luís Manzano, Francesc Formiga
Journal: European Journal of Heart Failure (2023)
Hepatitis C Treatment Initiation Among US Medicaid Enrollees
Authors: Shashi N. Kapadia, Hao Zhang, Christopher J. Gonzalez, Bisakha Sen, Ricardo Franco, Kayla Hutchings, Elaine Wethington, Andrew Talal, Audrey Lloyd, Arpan Dharia, Martin Wells, Yuhua Bao, Martin F Shapiro
Journal: JAMA Network Open (2023)

Importance Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection is highly effective but remains underused. Understanding disparities in the delivery of DAAs is important for HCV elimination planning and designing interventions to promote equitable treatment. Objective To examine variations in the receipt of DAA in the 6 months following a new HCV diagnosis. Design, Setting, and Participants This retrospective cohort study used national Medicaid claims from 2017 to 2019 from 50 states, Washington DC, and Puerto Rico. Individuals aged 18 to 64 years with a new diagnosis of HCV in 2018 were included. A new diagnosis was defined as a claim for an HCV RNA test followed by an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision ( ICD-10 ) diagnosis code, after a 1-year lookback period. Main Outcomes and Measures Outcome was receipt of a DAA prescription within 6 months of diagnosis. Logistic regression was used to examine demographic factors and ICD-10 –identified comorbidities associated with treatment initiation. Results Among 87 652 individuals, 43 078 (49%) were females, 12 355 (14%) were age 18 to 29 years, 35 181 (40%) age 30 to 49, 51 282 (46%) were non-Hispanic White, and 48 840 (49%) had an injection drug use diagnosis. Of these individuals, 17 927 (20%) received DAAs within 6 months of their first HCV diagnosis. In the regression analyses, male sex was associated with increased treatment initiation (OR, 1.24; 95% CI, 1.16-1.33). Being age 18 to 29 years (OR, 0.65; 95% CI, 0.50-0.85) and injection drug use (OR, 0.84; 95% CI, 0.75-0.94) were associated with decreased treatment initiation. After adjustment for state fixed effects, Asian race (OR, 0.50; 95% CI, 0.40-0.64), American Indian or Alaska Native race (OR, 0.68; 95% CI, 0.55-0.84), and Hispanic ethnicity (OR, 0.81; 95% CI, 0.71-0.93) were associated with decreased treatment initiation. Adjustment for state Medicaid policy did not attenuate the racial or ethnic disparities. Conclusions In this retrospective cohort study, HCV treatment initiation was low among Medicaid beneficiaries and varied by demographic characteristics and comorbidities. Interventions are needed to increase HCV treatment uptake among Medicaid beneficiaries and to address disparities in treatment among key populations, including younger individuals, females, individuals from minoritized racial and ethnic groups, and people who inject drugs.
Keeping IPMNs in Check: A Novel Role for the Transcription Factor NKX6-2 in Preserving an Indolent Cell Identity in Pancreatic Cystic Lesions
Authors: Aviad Ben-Shmuel, Ruth Scherz-Shouval
Journal: Cancer Discovery (2023)

Summary: In this issue of Cancer Discovery, Sans and colleagues identify the transcription factor NKX6-2 as a principal element in maintaining the low-grade gastric cell phenotype of intraductal papillary mucinous neoplasms (IPMN) in the pancreas. Their discoveries in patient cohorts and dissection in animal models provide a novel molecular understanding underpinning IPMN differentiation, with implications for risk stratification and therapeutic intervention in pancreatic cancer. See related article by Sans et al., p. 1844 (7).
A closer look at the role of iron in glioblastoma
Authors: Ganesh Shenoy, James R Connor
Journal: Neuro-Oncology (2023)

Abstract Glioblastoma (GBM) is among the deadliest malignancies facing modern oncology. While our understanding of certain aspects of GBM biology has significantly increased over the last decade, other aspects, such as the role of bioactive metals in GBM progression, remain understudied. Iron is the most abundant transition metal found within the earth’s crust and plays an intricate role in human physiology owing to its ability to participate in oxidation–reduction reactions. The importance of iron homeostasis in human physiology is apparent when examining the clinical consequences of iron deficiency or iron overload. Despite this, the role of iron in GBM progression has not been well described. Here, we review and synthesize the existing literature examining iron’s role in GBM progression and patient outcomes, as well as provide a survey of iron’s effects on the major cell types found within the GBM microenvironment at the molecular and cellular level. Iron represents an accessible target given the availability of already approved iron supplements and chelators. Improving our understanding of iron’s role in GBM biology may pave the way for iron-modulating approaches to improve patient outcomes.
Improved Labeling for “Transparent Mouse”
Journal: Cancer Discovery (2023)

Techniques for clearing mouse tissues or whole bodies and making them transparent are useful for anatomic analysis, but labeling specific cell types has been difficult. Researchers have developed a method, called wildDISCO, to highlight these cells and improve visualization of structural details. The technique uses a solvent to remove cholesterol from cell membranes in the mouse's body and employs conventional antibodies to tag the cells.
Protein and Peptide‐Based Nanotechnology for Enhancing Stability, Bioactivity, and Delivery of Anthocyanins
Authors: Lei Zhang, Liang Yao, Feng Zhao, Alice Yu, Yueru Zhou, Qingmei Wen, Jun Wang, Tao Zheng, Pu Chen
Journal: Advanced Healthcare Materials (2023)

Anthocyanin, a unique natural polyphenol, is abundant in plants and widely utilized in biomedicine, cosmetics, and the food industry due to its excellent antioxidant, anticancer, antiaging, antimicrobial, and anti-inflammatory properties. However, the degradation of anthocyanin in an extreme environment, such as alkali pH, high temperatures, and metal ions, limits its physiochemical stabilities and bioavailabilities. Encapsulation and combining anthocyanin with biomaterials could efficiently stabilize anthocyanin for protection. Promisingly, natural or artificially designed proteins and peptides with favorable stabilities, excellent biocapacity, and wide sources are potential candidates to stabilize anthocyanin. This review focuses on recent progress, strategies, and perspectives on protein and peptide for anthocyanin functionalization and delivery, i.e., formulation technologies, physicochemical stability enhancement, cellular uptake, bioavailabilities, and biological activities development. Interestingly, due to the simplicity and diversity of peptide structure, the interaction mechanisms between peptide and anthocyanin could be illustrated. This work sheds light on the mechanism of protein/peptide-anthocyanin nanoparticle construction and expands on potential applications of anthocyanin in nutrition and biomedicine.
Mineralocorticoid receptor antagonist use and the effects of empagliflozin on clinical outcomes in patients admitted for acute heart failure: Findings from <scp>EMPULSE</scp>
Authors: João Pedro Ferreira, Jonathan P. Blatchford, John R. Teerlink, Mikhail N. Kosiborod, Christiane E. Angermann, Jan Biegus, Sean P. Collins, Jasper Tromp, Michael E. Nassif, Mitchell A. Psotka, Josep Comin‐Colet, Robert J. Mentz, Martina Brueckmann, Matias Nordaby, Piotr Ponikowski, Adriaan A. Voors
Journal: European Journal of Heart Failure (2023)
NCI Rectal-Anal Task Force consensus recommendations for design of clinical trials in rectal cancer
Authors: Hagen F Kennecke, Rebecca Auer, May Cho, N Arvind Dasari, Cynthia Davies-Venn, Cathy Eng, Jennifer Dorth, Julio Garcia-Aguilar, Manju George, Karyn A Goodman, Lillian Kreppel, Joshua E Meyer, Jose Monzon, Leonard Saltz, Deborah Schrag, J Joshua Smith, Jason A Zell, Prajnan Das, Carmen Allegra, Hagen Kennecke, Rebecca Auer, Lillian Kreppel, Al Benson, Harvey Mamon, George Chang, Josh Meyer, May Cho, Jeff Meyerhardt, Prajnan Das, Jose Monzon, Arvind Dasari, Fang-Shu Ou, Dusty Deming, Lakshmi Rajdev, Jennifer Dorth, Jane Rogers, Cathy Eng, Lindsay Romak, George Fisher, Paul Romesser, Julio Garcia-Aguilar, Leonard Saltz, Manju George, Deborah Schrag, Thomas George, Arshin Sheybani, Karyn Goodman, Qian Shi, Vallerie Gordon, J Joshua Smith, William Hall, Noam VanderWalde, Atif Iqbal, Greg Yothers, Lisa Kachnic, Jason Zell
Journal: JNCI Journal of the National Cancer Institute (2023)

The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established. The task force achieved consensus on several areas, including the following: 1) the use of total neoadjuvant therapy with long-course radiation therapy either before or after chemotherapy, as well as short-course radiation therapy followed by chemotherapy, as the control arm of clinical trials; 2) the need for greater emphasis on patient involvement in treatment choices within the context of trial design; 3) efforts to identify those patients likely, or unlikely, to benefit from nonoperative management or minimally invasive surgery; 4) investigation of the utility of circulating tumor DNA measurements for tailoring treatment and surveillance; and 5) the need for identification of appropriate end points and recognition of challenges of data management for patients who enter nonoperative management trial arms. Substantial agreement was reached on priorities affecting the design of future clinical trials in patients with locally advanced rectal cancer.
Outbreak of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus in cats, Poland, June to July 2023
Authors: Katarzyna Domańska-Blicharz, Edyta Świętoń, Agnieszka Świątalska, Isabella Monne, Alice Fusaro, Karolina Tarasiuk, Krzysztof Wyrostek, Natalia Styś-Fijoł, Aleksandra Giza, Marta Pietruk, Bianca Zecchin, Ambra Pastori, Łukasz Adaszek, Małgorzata Pomorska-Mól, Grzegorz Tomczyk, Calogero Terregino, Stanisław Winiarczyk
Journal: Eurosurveillance (2023)

Background Over a 3-week period in late June/early July 2023, Poland experienced an outbreak caused by highly pathogenic avian influenza (HPAI) A(H5N1) virus in cats. Aim This study aimed to characterise the identified virus and investigate possible sources of infection. Methods We performed next generation sequencing and phylogenetic analysis of detected viruses in cats. Results We sampled 46 cats, and 25 tested positive for avian influenza virus. The identified viruses belong to clade 2.3.4.4b, genotype CH (H5N1 A/Eurasian wigeon/Netherlands/3/2022-like). In Poland, this genotype was responsible for several poultry outbreaks between December 2022 and January 2023 and has been identified only sporadically since February 2023. Viruses from cats were very similar to each other, indicating one common source of infection. In addition, the most closely related virus was detected in a dead white stork in early June. Influenza A(H5N1) viruses from cats possessed two amino acid substitutions in the PB2 protein (526R and 627K) which are two molecular markers of virus adaptation in mammals. The virus detected in the white stork presented one of those mutations (627K), which suggests that the virus that had spilled over to cats was already partially adapted to mammalian species. Conclusion The scale of HPAI H5N1 virus infection in cats in Poland is worrying. One of the possible sources seems to be poultry meat, but to date no such meat has been identified with certainty. Surveillance should be stepped up on poultry, but also on certain species of farmed mammals kept close to infected poultry farms.
Engineering of Uniform Epidermal Layers via Sacrificial Gelatin Bioink‐Assisted 3D Extrusion Bioprinting of Skin
Authors: Minjun Ahn, Won‐Woo Cho, Hanju Lee, Wonbin Park, Seok‐Hyeon Lee, Jae Woo Back, Qiqi Gao, Ge Gao, Dong‐Woo Cho, Byoung Soo Kim
Journal: Advanced Healthcare Materials (2023)

Abstract To reconstruct an ideal full‐thickness skin model, basal keratinocytes must be distributed as a confluent monolayer on the dermis. However, the currently available extrusion bioprinting method for the skin is limited when producing an air‐exposed cellular monolayer because the cells are encapsulated within a bioink. This is the first study to use sacrificial gelatin‐assisted extrusion bioprinting to reproduce a uniform and stratified epidermal layer. Experimental analyses of the rheological properties, printability, cell viability, and initial keratinocyte adhesion shows that the optimal gelatin bioink concentration is 4 wt.%. The appropriate thickness of the bioprinted gelatin structure for achieving a confluent keratinocyte layer is determined to be 400 µm. The suggested strategy generates a uniform keratinocyte monolayer with tight junctions throughout the central and peripheral regions, whereas manual seeding generates non‐uniform cellular aggregates and vacancies. These results influence gene expression, exhibiting a propensity for epidermal differentiation. Finally, the gelatin‐assisted keratinocytes are bioprinted onto a dermis composed of gelatin methacryloyl and dermis‐derived decellularized extracellular matrix to establish a full‐thickness skin model. Thus, this strategy leads to significant improvements in epidermal differentiation/stratification. The findings demonstrate that the gelatin‐assisted approach is advantageous for recreating reliable full‐thickness skin models with significant consistency for mass production.
Recent Advances in Antiarrhythmic Drug Therapy
Authors: Arnela Saljic, Jordi Heijman, Dobromir Dobrev
Journal: Drugs (2023)

Cardiac arrhythmias remain a common cause of death and disability. Antiarrhythmic drugs (AADs) and antiarrhythmic agents remain a cornerstone of current cardiac arrhythmia management, despite moderate efficacy and the potential for significant adverse proarrhythmic effects. Due to conceptual, regulatory and financial considerations, the number of novel antiarrhythmic targets and agents in the development pipeline has decreased substantially during the last few decades. However, several promising candidates remain and there are exciting developments in repurposing and reformulating already existing drugs for indications related to cardiac arrhythmias. This review discusses the key conceptual considerations for the development of new antiarrhythmic agents, summarizes new compounds and formulations currently in clinical development for rhythm control of atrial fibrillation, and highlights the potential for drug repurposing. Finally, future directions in AAD development are discussed. Together with an ever-increasing understanding of the molecular mechanisms underlying cardiac arrhythmias, these components support a cautiously optimistic outlook towards improved pharmacological treatment opportunities for patients suffering from cardiac arrhythmias.
Association Between Redlining and Spatial Access to Pharmacies
Authors: Giovanni Appolon, Shangbin Tang, Nico Gabriel, Jasmine Morales, Lucas A. Berenbrok, Jingchuan Guo, Inmaculada Hernandez
Journal: JAMA Network Open (2023)

This cross-sectional study evaluates whether there is an association between historic redlining and living within 1 or 2 miles of a pharmacy.
Centromere Plasticity With Evolutionary Conservation and Divergence Uncovered by Wheat 10+ Genomes
Authors: Huan Ma, Wentao Ding, Yiqian Chen, Jingwei Zhou, Wei Chen, Caixia Lan, Hailiang Mao, Qiang Li, Wenhao Yan, Handong Su
Journal: Molecular Biology and Evolution (2023)

Abstract Centromeres (CEN) are the chromosomal regions that play a crucial role in maintaining genomic stability. The underlying highly repetitive DNA sequences can evolve quickly in most eukaryotes, and promote karyotype evolution. Despite their variability, it is not fully understood how these widely variable sequences ensure the homeostasis of centromere function. In this study, we investigated the genetics and epigenetics of CEN in a population of wheat lines from global breeding programs. We captured a high degree of sequences, positioning, and epigenetic variations in the large and complex wheat CEN. We found that most CENH3-associated repeats are Cereba element of retrotransposons and exhibit phylogenetic homogenization across different wheat lines, but the less-associated repeat sequences diverge on their own way in each wheat line, implying specific mechanisms for selecting certain repeat types as functional core CEN. Furthermore, we observed that CENH3 nucleosome structures display looser wrapping of DNA termini on complex centromeric repeats, including the repositioned CEN. We also found that strict CENH3 nucleosome positioning and intrinsic DNA features play a role in determining centromere identity among different lines. Specific non-B form DNAs were substantially associated with CENH3 nucleosomes for the repositioned centromeres. These findings suggest that multiple mechanisms were involved in the adaptation of CENH3 nucleosomes that can stabilize CEN. Ultimately, we proposed a remarkable epigenetic plasticity of centromere chromatin within the diverse genomic context, and the high robustness is crucial for maintaining centromere function and genome stability in wheat 10+ lines as a result of past breeding selections.
Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling
Authors: Pailin Chiaranunt, Kyle Burrows, Louis Ngai, Siu Ling Tai, Eric Y. Cao, Helen Liang, Homaira Hamidzada, Anthony Wong, Julia Gschwend, Pascal Flüchter, Meggie Kuypers, Tijana Despot, Abdul Momen, Sung Min Lim, Thierry Mallevaey, Christoph Schneider, Tyrrell Conway, Hiromi Imamura, Slava Epelman, Arthur Mortha
Journal: Science Immunology (2023)

Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically guide intestinal MΦ development, although the exact nature, regulation, and location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated lymphoid tissues (SILTs) in a cell-extrinsic, NLRP3/P2X7R-dependent fashion in the steady state. Tissue-infiltrating monocytes accumulating around SILTs followed a spatially constrained, distinct developmental trajectory into SILT-associated MΦs (SAMs). CSF2 regulated the mitochondrial membrane potential and reactive oxygen species production of SAMs and contributed to the antimicrobial defense against enteric bacterial infections. Collectively, these findings identify SILTs and CSF2-producing ILC3s as a microanatomic niche for intestinal MΦ development and functional programming fueled by the integration of commensal microbial energy metabolism.
1-Oleoyl-lysophosphatidylethanolamine stimulates RORγt activity in T <sub>H</sub> 17 cells
Authors: Yusuke Endo, Toshio Kanno, Takahiro Nakajima, Kazutaka Ikeda, Yoshitaka Taketomi, Satoru Yokoyama, Shigemi Sasamoto, Hikari K. Asou, Keisuke Miyako, Yoshinori Hasegawa, Yusuke Kawashima, Osamu Ohara, Makoto Murakami, Toshinori Nakayama
Journal: Science Immunology (2023)

Metabolic fluxes involving fatty acid biosynthesis play essential roles in controlling the differentiation of T helper 17 (T H 17) cells. However, the exact enzymes and lipid metabolites involved, as well as their link to promoting the core gene transcriptional signature required for the differentiation of T H 17 cells, remain largely unknown. From a pooled CRISPR-based screen and unbiased lipidomics analyses, we identified that 1-oleoyl-lysophosphatidylethanolamine could act as a lipid modulator of retinoid-related orphan receptor gamma t (RORγt) activity in T H 17 cells. In addition, we specified five enzymes, including Gpam , Gpat3 , Lplat1 , Pla2g12a , and Scd2 , suggestive of the requirement of glycerophospholipids with monounsaturated fatty acids being required for the transcription of Il17a . 1-Oleoyl-lysophosphatidylethanolamine was reduced in Pla2g12a -deficient T H 17 cells, leading to the abolition of interleukin-17 (IL-17) production and disruption to the core transcriptional program required for the differentiation of T H 17 cells. Furthermore, mice with T cell–specific deficiency of Pla2g12a failed to develop disease in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Thus, our data indicate that 1-oleoyl-lysophosphatidylethanolamine is a lipid metabolite that promotes RORγt-induced T H 17 cell differentiation and the pathogenicity of T H 17 cells.
Dramatic efficacy of cannabidiol on refractory chronic pain in an adolescent with sickle cell disease
Authors: Lara Mayrand, Anne‐Laure Tarbé de Saint Hardouin, Thiago Trovati Maciel, Rachel Rignault‐Bricard, Melissa Taylor, Joséphine Brice, Mariane de Montalembert, Olivier Hermine, Céline Greco, Slimane Allali
Journal: American Journal of Hematology (2023)

Here, we report a dramatic efficacy of cannabidiol in an adolescent with SCD suffering from chronic pain refractory to other analgesics, with complete regression of chronic pain and rapid plasma histamine level normalization after treatment.
Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis: Toward a precision therapy
Authors: Weixuan Liu, Anqi Liu, Xujun Li, Ziyang Sun, Zhenghua Sun, Yaru Liu, Gang Wang, Dan Huang, Hao Xiong, Shiyang Yu, Xintao Zhang, Cunyi Fan
Journal: Bioactive Materials (2023)

Osteoarthritis (OA) is the most common disabling joint disease with no effective disease modifying drugs. Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models, representing a novel therapeutic strategy. In this study, we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-EVs) could maintain chondrocyte homeostasis and alleviate OA, and further revealed a novel molecular mechanism of this therapeutic effect. miR-223, which could directly bind with the 3'UTR of NLRP3 mRNA, was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting. For enhancing the effect on mitigating osteoarthritis, exogenous miR-223 was loaded into hUC-EVs by electroporation, and a collagen II-targeting peptide (WYRGRL) was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage. The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis, and offered excellent results for the treatment of OA. This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.